Project Summary/Abstract The developing gustatory system is characterized by impressive structural and functional changes. The central taste pathway in rodents is especially plastic during normal development, even at the first synaptic relay. Structurally, the terminations (i.e., terminal fields) of neurons carrying taste information from taste buds to the nucleus of the solitary tract (NST) in the medulla are reduced in size, or ?pruned?, to about half of their size -- beginning just before weaning and extending for about 10 days after weaning. Functionally, the period of ?pruning? occurs coincident with the increase in taste-elicited neural activity in gustatory nerves, suggesting a requisite activity-dependent component. Moreover, experimental manipulations of neural activity and the animal?s dietary history during development interrupts the normal ?pruning? of terminal fields, indicating that both activity-dependent and activity-independent factors play a role in the developmental process of circuit refinement. The long-term goal of this project is to understand how the central gustatory system is assembled and then refined by experience. The specific aims of this proposal examine 1) how neurons that innervate single taste buds on the anterior 2/3 of the tongue map onto the NST and how the projections change during normal development and in adult mice that have altered neural activity throughout development or an altered dietary history, and 2) how the neuro-immune molecular cascade operating during normal development is interrupted in mice that have altered neural activity or an altered dietary history. The aims of the project will be addressed through coordinated techniques of single taste bud labels, peripheral taste nerve recordings, central nervous system tract tracing, extensive analyses of synaptic elements at the light and electron microscopic level, and optogenetic recovery of function experiments. These studies will provide new and important information about the development and plasticity of the central gustatory system, the interplay between the immune and gustatory systems during development, and more broadly, they will be useful in determining the role that the maternal diet and taste-elicited activity have on organizing the developing sense of taste.